Caponetti, Angelo Giuseppe
(2024)
Characterization and natural history of different phenotypes in hereditary transthyretin amyloidosis: 40-year experience at a single Italian referral center, [Dissertation thesis], Alma Mater Studiorum Università di Bologna.
Dottorato di ricerca in
Scienze cardio nefro toraciche, 36 Ciclo. DOI 10.48676/unibo/amsdottorato/11347.
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Abstract
- Aims: Hereditary Transthyretin Amyloidosis (ATTRv) is one of the leading etiologies of systemic amyloidosis with more than 135 mutations described and a broad spectrum of clinical manifestations. We aimed to provide a systematic description of a population of individuals carrying pathogenic mutations of transthyretin (TTR) gene and to investigate the major clinical events during follow up.
- Methods: Observational, retrospective, cohort study including consecutive patients with mutations of TTR gene, admitted to a tertiary referral center in Bologna, Italy, between 1984 and 2022.
- Results: Three hundred twenty-five patients were included: 106 asymptomatic carriers, 49 cardiac phenotype, 49 neurological phenotype and 121 mixed phenotype. Twenty-three different mutations were found, with Ile68Leu (41.8%), Val30Met (19%), and Glu89Gln (10%) being the most common. After a median follow-up of 51 months data from 290 subjects were analyzed; among them 111 (38.3%) died and 123 (42.4%) had a major clinical event (death or hospitalization for heart failure). Nine (11.5%) of the 78 asymptomatic carriers showed signs and symptoms of the disease. Carriers had a prognosis comparable to healthy population, while no significant differences were seen among the three phenotypes adjusted by age. Age at diagnosis, NYHA functional class, left ventricular ejection fraction, mPND score and disease-modifying therapy were independently associated with survival.
- Conclusions: This study offers a wide and comprehensive overview of ATTRv from the point of view of a tertiary referral center in Italy. Three main phenotypes can be identified (cardiac, neurological and mixed) with specific clinical and instrumental features. Family screening programs are essential to identify paucisymptomatic affected patients or unaffected carriers of the mutation, to be followed through the years. Lastly, disease-modifying therapy represents an evolving cornerstone of the management of ATTRv, with a great impact on mortality.
Abstract
- Aims: Hereditary Transthyretin Amyloidosis (ATTRv) is one of the leading etiologies of systemic amyloidosis with more than 135 mutations described and a broad spectrum of clinical manifestations. We aimed to provide a systematic description of a population of individuals carrying pathogenic mutations of transthyretin (TTR) gene and to investigate the major clinical events during follow up.
- Methods: Observational, retrospective, cohort study including consecutive patients with mutations of TTR gene, admitted to a tertiary referral center in Bologna, Italy, between 1984 and 2022.
- Results: Three hundred twenty-five patients were included: 106 asymptomatic carriers, 49 cardiac phenotype, 49 neurological phenotype and 121 mixed phenotype. Twenty-three different mutations were found, with Ile68Leu (41.8%), Val30Met (19%), and Glu89Gln (10%) being the most common. After a median follow-up of 51 months data from 290 subjects were analyzed; among them 111 (38.3%) died and 123 (42.4%) had a major clinical event (death or hospitalization for heart failure). Nine (11.5%) of the 78 asymptomatic carriers showed signs and symptoms of the disease. Carriers had a prognosis comparable to healthy population, while no significant differences were seen among the three phenotypes adjusted by age. Age at diagnosis, NYHA functional class, left ventricular ejection fraction, mPND score and disease-modifying therapy were independently associated with survival.
- Conclusions: This study offers a wide and comprehensive overview of ATTRv from the point of view of a tertiary referral center in Italy. Three main phenotypes can be identified (cardiac, neurological and mixed) with specific clinical and instrumental features. Family screening programs are essential to identify paucisymptomatic affected patients or unaffected carriers of the mutation, to be followed through the years. Lastly, disease-modifying therapy represents an evolving cornerstone of the management of ATTRv, with a great impact on mortality.
Tipologia del documento
Tesi di dottorato
Autore
Caponetti, Angelo Giuseppe
Supervisore
Dottorato di ricerca
Ciclo
36
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
amyloidosis, transthyretin, healthy carriers, cardiomyopathy, polyneuropathy
URN:NBN
DOI
10.48676/unibo/amsdottorato/11347
Data di discussione
22 Marzo 2024
URI
Altri metadati
Tipologia del documento
Tesi di dottorato
Autore
Caponetti, Angelo Giuseppe
Supervisore
Dottorato di ricerca
Ciclo
36
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
amyloidosis, transthyretin, healthy carriers, cardiomyopathy, polyneuropathy
URN:NBN
DOI
10.48676/unibo/amsdottorato/11347
Data di discussione
22 Marzo 2024
URI
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